We have recently reported a unique minimal residual disease model in which 75% of W/Fu rats recur within 4-22 weeks after "curative" resection of chemically induced primary bowel adenocarcinomas. Immunization with irradiated colon tumor isografts sharing "tissue-type specificity" decreased local/regional recurrence significantly in multiple in vivo experiments compared to nonimmunized controls or compared to animals immunized with non-"tissue-type specific" isografts after primary tumor resection. The goal of this grant will be to use this new minimal residual disease model to study adjuvant therapy with potential applicability to humans with colon cancer. First, we will attempt to detail the kinetics of our already effective adjuvant immunization protocols. Isograft tumors with differing histology, immunogenicity, and growth characteristics will be tested in comparison to the "tissue-type specific" isograft tumor already shown to be effective. Enhancement of immunoprotection by adult thymectomy performed at the time of primary tumor resection with or without subsequent immunization will be tested. Effectiveness of allogeneic rat colon carcinoma immunization in protecting against recurrence will be tested as the next step in transition to a system more compatible with potential human trials. Mechanisms of host response in this minimal residual disease scheme will be examined including quantitation of serial changes in host immune complex concentration using a newly designed nonspecific immune complex assay that we have recently applied to the minimal residual disease model and to humans with gestational trophoblastic neoplasia. We will also include newly defined antigen specific immune complex quantitation in serial sera sampling in the minimal residual disease model. In addition, newly available monoclonal antibodies for marking rat lymphocyte subsets will be used to quantitate peripheral lymphocyte subset changes before and after carcinogen exposure, before and after immunization, and at the time of regional tumor recurrence. Intramural accumulations of lymphocytes in the bowel wall adjacent to tumor recurrence will also be quantitated by serial section of the large intestine.